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Objectives This study aims to evaluate the effects of preoperative melatonin along with intraoperative total intravenous anaesthesia (TIVA) on the Quality of Recovery (QoR) score (primary objective) and preoperative anxiety and post-surgical pain (secondary objectives) in patients undergoing spine surgery.Design Prospective randomised exploratory study.Setting Operation theatre and ward.Participants Patients undergoing spine surgery under intraoperative neuromonitoring.Intervention and outcome measures 70 patients of either sex, American Society of Anaesthesiology I-II, undergoing elective spine surgery with intraoperative neuro-physiological monitoring were selected and administered either tablet melatonin 5 mg (Group I) or placebo (Group II) the night before and 2 hours before surgery. Anaesthesia in all cases was maintained with TIVA using propofol infusion (100–150 µg/kg/min), fentanyl (2 µg/kg/hour) and dexmedetomidine (1 µg/kg over 15 min followed by 0.5 µg/kg/min) to maintain a Bispectral Index of 40–60. Preoperative anxiety and sedation, postoperative pain and QoR were evaluated preoperatively and at different time intervals in the postoperative period.Results Demographic profile was comparable. Median anxiety score as assessed by Ramsay’s sedation/anxiety score was two in (group I) and Group II, respectively. No statistical differences in total intraoperative dosage of propofol, dexmedetomidine and fentanyl were observed (p>0.05) in either group. Median Visual Analogue Score at 6 hours postoperatively was 3 (3–4) (group I) and 6 (5–7) in Group II, respectively. QoR 15 scores (Group I vs Group II) were 99.34 (3.08) versus 89.46 (4.31) at 1 hour, 112.37 (3.75) versus 101.37 (4.86) at 6 hours and 123.23 (3.38) versus 113.03 (4.46) at 24 hours, respectively. QoR scores were higher in Group I compared with Group II (p<0.001) at all time points. Thus, it showed better QoR in patients receiving melatonin premedication, without any significant effect on preoperative anxiety.Conclusion Use of preoperative melatonin is associated with a favourable influence on postoperative pain and QoR scores, thus improving postoperative recovery.Trial registration number CTRI/2020/11/029002).